The present invention relates generally to methods and apparatus for treating or controlling medical, psychiatric or neurological disorders by application of modulating electrical signals to a selected nerve or nerve bundle, and more particularly to techniques for treating patients with eating disorders by application of such signals to the patient's vagus nerve with a neurostimulating device.
Treatment of obesity attributable to compulsive overeating has included many different schemes in the past. Among these is the use of ethical (or prescription) and patent (or nonprescription) drugs or other ingestible preparations designed to suppress the appetite or to induce satiety (i.e., the satisfied feeling of being full after eating). Another type of treatment employs dietary menus selected to reduce caloric intake, often combined with a regimen of routine or aerobic exercise. An increasingly popular treatment is liposuction (suction lipectomy), at one time prescribed almost exclusively only for removing adipose tissue from obese patients, but more recently enjoying wide application for cosmetic reshaping of the anatomy, particularly the abdomen, hips, thighs and buttocks of non-obese persons. In advanced or extreme cases, treatment of obesity has included more radical techniques such stapling or resectioning of the stomach, or wiring the jaws shut.
In general, these and other prior art techniques for treating compulsive overeating/obesity have tended to produce only a temporary effect. After the initial weight loss and typical plateauing of further loss, the individual usually becomes discouraged and/or depressed, and reverts to the previous behavior of compulsive overeating. The more radical techniques employed for treating the extreme cases are sufficiently drastic to warrant consideration of methods which are less intrusive and more easily tolerated by the patient. Even stomach stapling and resection have been found to produce only short term benefit.
The present invention is primarily directed to methods and devices for stimulation of the vagus nerve to treat compulsive overeating and obesity, but which may be employed to treat other, even more serious eating disorders, such as bulimia (a disorder in which the individual experiences periods of insatiable craving for food, often resulting in episodes of binge eating followed by forced vomiting) and anorexia nervosa (a neuropsychiatric disorder in which the individual suffers a prolonged and sometimes fatal refusal to eat), as well. The treatment is characterized by the application of selected electrical stimuli to the vagus nerve or a bundle of nerve fibers thereof.
Food intake is controlled by a complex interaction of internal and external stimuli. The vagus nerve plays a role in mediating afferent information from the stomach to the satiety center of the brain. Davidson and Clarke reported in Am. J. Physiol. (1988) 255:G55-G61, their findings that afferent vagal fibers from the stomach wall increased their firing rate when the stomach was filled. This satiety effect is known to be mediated by cholecystokinin (CCK) and pancreatic glucagon, as shown by Sauter and Geary in J. Auton. Nerv. Syst. (1990) 30:13-22. In Neuropharmacol. (1990) 29(2):109-118, Schick et al reported on experiments conducted in animals that the central receptors for CCK reside in the nucleus of the solitary tract, which are the projection sites for the vagus nerve. This is also the case in humans, as indicated by Hyde and Peroutka in their report in Brain Res. (1989) 495:198-202. Weatherford and Ritter, in Physiol. and Behav. (1988) 43:645-650, further showed that glucagon mediated satiety involves separate cells in contrast to CCK mediated satiety in the nucleus of the solitary tract and area postrema.
Peikin in Gastroenterol. Clinics of North America (1989) 18(4):757-775 has reviewed the role of CCK in the control of food intake, and the potential use of CCK and analogues in the treatment of eating disorders. Although the focus has been on the possibility of up-modulating CCK activity for the treatment of obesity and bulimia, decreasing CCK activity for treatment of anorexia is also a possibility.
Extra-physiologic electrical stimulation of the vagus nerve has previously been proposed for treatment of epilepsy and various forms of involuntary movement disorders. Specifically, in U.S. Pat. No. 4,702,254 issued Oct. 27, 1987 to J. Zabara (referred to herein as "the '254 patent"), a method and implantable device are disclosed for alleviating or preventing epileptic seizures, characterized by abnormal neural discharge patterns of the brain. The '254 patent describes an implantable neurocybernetic prosthesis (NCP) which utilizes neurocybernetic spectral discrimination by tuning the external current of the NCP generator to the electrochemical properties of a specific group of inhibitory neurons that affect the reticular system of the brain. These neurons are embedded within a bundle of other neurons, and are selectively activated directly or indirectly by the tuning of the NCP to augment states of brain neural discharge to control convulsions or seizures. According to the patent, the spectral discrimination analysis dictates that certain electrical parameters of the NCP pulse generator be selected based on the electrochemical properties of the nerves desired to be activated. The patent further indicates that the optimum sites for application of the NCP generator output to produce the desired effects are the cranial nerves in general, and the vagus nerve (the tenth cranial nerve) in particular.
The NCP disclosed in the '254 patent may be activated either manually or automatically, to provide treatment for the duration of the seizure. Manual activation is performed when the patient experiences the aura at onset of the seizure. Alternatively, automatic activation may be triggered upon detection of instantaneous changes in certain state parameters immediately preceding or at onset. Additionally, a "prophylactic" or preventive mode may be employed in which the NCP is activated periodically to reduce the occurrence and/or the intensity of the seizures.
The NCP stimulator of the '254 patent is implanted in the patient's chest and is connected to electrodes installed at the selected point of signal application at the nerve site with the more negative electrode situated closer to the brain and the positive electrode further from the brain, along the vagus nerve.
It is known that each nerve in the human body is composed of thousands of fibers, of different sizes designated by groups A, B and C, which carry signals to and from the brain. The vagus nerve, for example, may have approximately 100,000 fibers of the three different sizes, each carrying signals. Each axon (fiber) only conducts in one direction, in normal circumstances. The A and B fibers are myelinated (i.e., have a myelin sheath, constituting a substance largely composed of fat), whereas the C fibers are unmyelinated.
Myelinated fibers are typically larger, conduct faster and have very low stimulation thresholds, compared to the unmyelinated type. Very little energy is required to stimulate the myelinated fibers, and they exhibit a particular strength-duration curve or respond to a specific pulse width versus amplitude for stimulation. The A and B fibers can be stimulated with relatively narrow pulse widths, from 50 to 200 microseconds (us), for example. The A fiber conducts slightly faster than the B fiber and has a slightly lower threshold. The C fibers are very small, conduct electrical signals very slowly, and have high stimulation thresholds typically requiring a wider pulse width (300-1000 us) and a higher amplitude for activation. Selective stimulation of only A and B fibers is readily accomplished. The requirement of a larger and wider pulse to stimulate the C fibers, however, makes selective stimulation of only C fibers, to the exclusion of the A and B fibers, virtually unachievable inasmuch as the large signal will tend to activate the A and B fibers to some extent as well.
Usually, nerve stimulation activates signals in both directions (bidirectionally). It is possible, however, through the use of special electrodes and waveforms, to selectively stimulate a nerve in one direction only (unidirectionally).
In a paper on the effects of vagal stimulation on experimentally induced seizures in rats (Epilepsia 1990, 31 (Supp 2): S7-S19), Woodbury notes that the vagus nerve is composed of somatic and visceral afferents (inward conducting nerve fibers that convey impulses toward a nerve center such as the brain or spinal cord) and efferents (outward conducting nerve fibers that convey impulses to an effector to stimulate same and produce activity). The vast majority of vagal nerve fibers are C fibers, and a majority are visceral afferents having cell bodies lying in masses or ganglia in the neck. The central projections terminate, by and large, in the nucleus of the solitary tract which sends fibers to various regions of the brain (e.g., the hypothalamus, thalamus, and amygdala); others continue to the medial reticular formation of the medulla, the cerebellum, the nucleus cuneatus and other regions.